let-7 regulates Dicer expression and constitutes a negative feedback loop

Shogo Tokumaru, Motoshi Suzuki, Hideki Yamada, Masato Nagino, Takashi Takahashi

Research output: Contribution to journalArticle

162 Citations (Scopus)

Abstract

microRNAs (miRNA) are small, endogenously expressed non-coding RNAs that are sequentially processed by Drosha and Dicer from primary transcripts, by negatively regulating the expression of protein-coding genes through either translational repression or RNA degradation. Their expression patterns are developmentally regulated and/or tissue specific, while altered expressions of certain miRNAs are frequently observed in human cancers, though the underlying regulatory mechanism is largely unknown. Herein, we show that Dicer expression was inversely correlated with expression levels of mature let-7 in a panel of human cancer cell lines, showing association with cell growth and cell cycle phases. Overexpression of let-7 significantly reduced the expression of Dicer at both the protein and messenger RNA levels, whereas antisense-mediated reduction of let-7 expression conversely increased Dicer at both levels. A luciferase assay using a reporter carrying a putative target site in the 3′ untranslated region of Dicer revealed that let-7 directly affects Dicer expression. Downregulation of Dicer resulted in a reduced expression of mature let-7. Furthermore, overexpression of let-7 decreased the levels of expression of other mature miRNAs, while knockdown of let-7 increased those levels. Taken together, these findings strongly suggest the possible existence of a novel regulatory loop, in which let-7 may play a role as a key miRNA for implementing the tightly regulated, equilibrated state of Dicer and various miRNAs.

Original languageEnglish
Pages (from-to)2073-2077
Number of pages5
JournalCarcinogenesis
Volume29
Issue number11
DOIs
Publication statusPublished - 19-11-2008
Externally publishedYes

Fingerprint

MicroRNAs
Untranslated RNA
RNA Stability
3' Untranslated Regions
Luciferases
Neoplasms
Cell Cycle
Proteins
Down-Regulation
Cell Line
Messenger RNA
Growth

All Science Journal Classification (ASJC) codes

  • Cancer Research

Cite this

Tokumaru, Shogo ; Suzuki, Motoshi ; Yamada, Hideki ; Nagino, Masato ; Takahashi, Takashi. / let-7 regulates Dicer expression and constitutes a negative feedback loop. In: Carcinogenesis. 2008 ; Vol. 29, No. 11. pp. 2073-2077.
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abstract = "microRNAs (miRNA) are small, endogenously expressed non-coding RNAs that are sequentially processed by Drosha and Dicer from primary transcripts, by negatively regulating the expression of protein-coding genes through either translational repression or RNA degradation. Their expression patterns are developmentally regulated and/or tissue specific, while altered expressions of certain miRNAs are frequently observed in human cancers, though the underlying regulatory mechanism is largely unknown. Herein, we show that Dicer expression was inversely correlated with expression levels of mature let-7 in a panel of human cancer cell lines, showing association with cell growth and cell cycle phases. Overexpression of let-7 significantly reduced the expression of Dicer at both the protein and messenger RNA levels, whereas antisense-mediated reduction of let-7 expression conversely increased Dicer at both levels. A luciferase assay using a reporter carrying a putative target site in the 3′ untranslated region of Dicer revealed that let-7 directly affects Dicer expression. Downregulation of Dicer resulted in a reduced expression of mature let-7. Furthermore, overexpression of let-7 decreased the levels of expression of other mature miRNAs, while knockdown of let-7 increased those levels. Taken together, these findings strongly suggest the possible existence of a novel regulatory loop, in which let-7 may play a role as a key miRNA for implementing the tightly regulated, equilibrated state of Dicer and various miRNAs.",
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Tokumaru, S, Suzuki, M, Yamada, H, Nagino, M & Takahashi, T 2008, 'let-7 regulates Dicer expression and constitutes a negative feedback loop', Carcinogenesis, vol. 29, no. 11, pp. 2073-2077. https://doi.org/10.1093/carcin/bgn187

let-7 regulates Dicer expression and constitutes a negative feedback loop. / Tokumaru, Shogo; Suzuki, Motoshi; Yamada, Hideki; Nagino, Masato; Takahashi, Takashi.

In: Carcinogenesis, Vol. 29, No. 11, 19.11.2008, p. 2073-2077.

Research output: Contribution to journalArticle

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AU - Suzuki, Motoshi

AU - Yamada, Hideki

AU - Nagino, Masato

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